Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression
Non-muscle-invasive bladder cancer (NMIBC) consists of transcriptional subtypes that are distinguishable from those of muscle-invasive cancer. We aimed to identify genetic signatures of NMIBC related to basal (K5/6) and luminal (K20) keratin expression. Based on immunohistochemical staining, papilla...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/20/7726 |
| _version_ | 1797550503210516480 |
|---|---|
| author | Minsun Jung Insoon Jang Kwangsoo Kim Kyung Chul Moon |
| author_facet | Minsun Jung Insoon Jang Kwangsoo Kim Kyung Chul Moon |
| author_sort | Minsun Jung |
| collection | DOAJ |
| description | Non-muscle-invasive bladder cancer (NMIBC) consists of transcriptional subtypes that are distinguishable from those of muscle-invasive cancer. We aimed to identify genetic signatures of NMIBC related to basal (K5/6) and luminal (K20) keratin expression. Based on immunohistochemical staining, papillary high-grade NMIBC was classified into K5/6-only (K5/6<sup>High</sup>-K20<sup>Low)</sup>, K20-only (K5/6<sup>Low</sup>-K20<sup>High</sup>), double-high (K5/6<sup>High</sup>-K20<sup>High</sup>), and double-low (K5/6<sup>Low</sup>-K20<sup>Low</sup>) groups (<i>n</i> = 4 per group). Differentially expressed genes identified between each group using RNA sequencing were subjected to functional enrichment analyses. A public dataset was used for validation. Machine learning algorithms were implemented to predict our samples against UROMOL subtypes. Transcriptional investigation demonstrated that the K20-only group was enriched in the cell cycle, proliferation, and progression gene sets, and this result was also observed in the public dataset. The K5/6-only group was closely regulated by basal-type gene sets and showed activated invasive or adhesive functions. The double-high group was enriched in cell cycle arrest, macromolecule biosynthesis, and <i>FGFR3</i> signaling. The double-low group moderately expressed genes related to cell cycle and macromolecule biosynthesis. All K20-only group tumors were classified as UROMOL “class 2” by the machine learning algorithms. K5/6 and K20 expression levels indicate the transcriptional subtypes of NMIBC. The K5/6<sup>Low</sup>-K20<sup>High</sup> expression is a marker of high-risk NMIBC. |
| first_indexed | 2024-03-10T15:30:14Z |
| format | Article |
| id | doaj.art-1439caffc8614225a31c1c173ef53fac |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:30:14Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1439caffc8614225a31c1c173ef53fac2023-11-20T17:39:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120772610.3390/ijms21207726Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin ExpressionMinsun Jung0Insoon Jang1Kwangsoo Kim2Kyung Chul Moon3Department of Pathology, Seoul National University College of Medicine, Seoul 03080, KoreaBiomedical Research Institute, Seoul National University Hospital, Seoul 03080, KoreaTransdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul 03080, KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, KoreaNon-muscle-invasive bladder cancer (NMIBC) consists of transcriptional subtypes that are distinguishable from those of muscle-invasive cancer. We aimed to identify genetic signatures of NMIBC related to basal (K5/6) and luminal (K20) keratin expression. Based on immunohistochemical staining, papillary high-grade NMIBC was classified into K5/6-only (K5/6<sup>High</sup>-K20<sup>Low)</sup>, K20-only (K5/6<sup>Low</sup>-K20<sup>High</sup>), double-high (K5/6<sup>High</sup>-K20<sup>High</sup>), and double-low (K5/6<sup>Low</sup>-K20<sup>Low</sup>) groups (<i>n</i> = 4 per group). Differentially expressed genes identified between each group using RNA sequencing were subjected to functional enrichment analyses. A public dataset was used for validation. Machine learning algorithms were implemented to predict our samples against UROMOL subtypes. Transcriptional investigation demonstrated that the K20-only group was enriched in the cell cycle, proliferation, and progression gene sets, and this result was also observed in the public dataset. The K5/6-only group was closely regulated by basal-type gene sets and showed activated invasive or adhesive functions. The double-high group was enriched in cell cycle arrest, macromolecule biosynthesis, and <i>FGFR3</i> signaling. The double-low group moderately expressed genes related to cell cycle and macromolecule biosynthesis. All K20-only group tumors were classified as UROMOL “class 2” by the machine learning algorithms. K5/6 and K20 expression levels indicate the transcriptional subtypes of NMIBC. The K5/6<sup>Low</sup>-K20<sup>High</sup> expression is a marker of high-risk NMIBC.https://www.mdpi.com/1422-0067/21/20/7726non-muscle-invasive bladder cancerurinary bladder neoplasmsgene expression profilingkeratin-5/6keratin-20biomarkers |
| spellingShingle | Minsun Jung Insoon Jang Kwangsoo Kim Kyung Chul Moon Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression International Journal of Molecular Sciences non-muscle-invasive bladder cancer urinary bladder neoplasms gene expression profiling keratin-5/6 keratin-20 biomarkers |
| title | Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression |
| title_full | Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression |
| title_fullStr | Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression |
| title_full_unstemmed | Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression |
| title_short | Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression |
| title_sort | non muscle invasive bladder carcinoma with respect to basal versus luminal keratin expression |
| topic | non-muscle-invasive bladder cancer urinary bladder neoplasms gene expression profiling keratin-5/6 keratin-20 biomarkers |
| url | https://www.mdpi.com/1422-0067/21/20/7726 |
| work_keys_str_mv | AT minsunjung nonmuscleinvasivebladdercarcinomawithrespecttobasalversusluminalkeratinexpression AT insoonjang nonmuscleinvasivebladdercarcinomawithrespecttobasalversusluminalkeratinexpression AT kwangsookim nonmuscleinvasivebladdercarcinomawithrespecttobasalversusluminalkeratinexpression AT kyungchulmoon nonmuscleinvasivebladdercarcinomawithrespecttobasalversusluminalkeratinexpression |